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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 55 records · Page 3Linked to original sources

Incorporation of diaphyseal sequestra in chronic haematogenous osteomyelitis.

Seventeen patients with haematogenous osteomyelitis and long diaphyseal sequestra are reported. Treatment was incision and drainage with antibiotics for at least 6 to 8 weeks, the limb being protected in plaster for a long time. The sequestra became incorporated in every case. Sequestrectomy should only be undertaken when successive radiographs show no reduction in size of the sequestrum and an increase in the amount of the involucrum.

Adolescent

Lead "bursogram" and focal synovitis secondary to a retained intraarticular bullet fragment.

We present an unusual case in which retained lead bullet in the wrist joint dissolved and migrated into a synovial recess, producing reactive focal synovitis. The clinical presentation suggested a soft tissue mass or ganglion cyst. The radiologic findings of dense metallic fragments within a recess of the wrist joint established the correct diagnosis and excluded other causes of soft tissue masses. Radiologic recognition of retained intra-articular lead fragments is important, as the clinical features of systemic lead intoxication, lead arthopathy, or reactive focal synovitis may be subtle or misleading.

Adult

Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms.

Developmentally regulated mouse gene Nedd2 encodes a protein similar to the product of the nematode Caenorhabditis elegans cell death gene ced-3 and the mammalian interleukin-1 beta-converting enzyme. Overexpression of Nedd2 in cultured mammalian cells induces apoptosis that can be blocked by proto-oncogene BCL2. We have isolated cDNA clones for the human homologue of the mouse gene and, by using these as probes, mapped the human NEDD2 gene to 7q34-35 by fluorescence in situ hybridisation. The potential tumour suppressor function of NEDD2 is discussed.

Apoptosis

Assignment of the developmentally regulated gene NEDD1 to human chromosome 12q22 by fluorescence in situ hybridization.

The developmentally regulated mouse gene Nedd 1 encodes a protein showing similarities with the beta-subunit of heterotrimeric GTP-binding proteins and has growth suppressing activity when overexpressed in various cultured cell types. We have mapped the human homolog (NEDD1) of the mouse gene to chromosome 12q22 by fluorescence in situ hybridization using R-banded human (pro)metaphase chromosomes.

Animals

Differentiation of human osteoblastic cells in culture: modulation of proteases by extracellular matrix and tumor necrosis factor-alpha.

We have followed the synthesis and secretion of urokinase-type plasminogen activator (u-PA) and its inhibitor, PAI-1, and matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP-1) during differentiation of a human osteoblastic cell line, HOS TE85, and the effect of TNF-alpha on this process. Our results show that the ratio of u-PA/PAI-1 associated with the cell-matrix components increases during differentiation of these cells over a 14-day period. Although TNF-alpha suppresses the induced increase in steady-state mRNA levels of u-PA and PAI-1 during maturation of extracellular matrix (ECM), the u-PA/PAI-1 ratio is altered in such a way that PA activity associated with the ECM is higher than control cells. The expression of MMP-1 is low and remains essentially invariant over a culture period of 14 days. TNF-alpha enhances MMP-1 transcription nearly 12-fold initially, after which mRNA levels drop off but remain significantly higher than the controls. Activities and steady-state mRNA levels of MMP-2 and MMP-9 increase nearly 15-fold during maturation of the ECM, but the level of TIMP-1 mRNA is not appreciably altered. The presence of TNF-alpha suppresses maturation-induced transcription of MMP-2, enhances TIMP-1 transcription, but has little effect on MMP-9 mRNA levels. The data show that chronic exposure to TNF-alpha alters the balance between u-PA/PAI-1 and MMPs/TIMP-1, which favors higher activity of proteinases. Accordingly, the presence of TNF-alpha in chronic inflammatory episodes would be expected to alter bone remodeling by inhibiting maturation of ECM and formation of bone.

Cell Differentiation

Characterization of human and rat immortalized clones parotid acinar cells with respect to specific proteins and their mRNAs, and receptor-linked adenylate cyclase.

This study reports the isolation and characterization of a rat nontumorigenic parotid acinar cell clone (2RSG), a human nontumorigenic parotid acinar cell clone (2HPC8), and a human tumorigenic acinar clone (2HP1G). The levels of alpha-amylase mRNAs detected when using alpha-amylase cDNA of 1176 and 702 bp for hybridization were higher in 2RSG and 2HPC8 cells than their respective whole parotid glands. The level of these mRNAs decreased in 2HP1G cells. In contrast to alpha-amylase mRNAs levels, the alpha-amylase activity in cultured acinar cells was extremely low in comparison to whole glands, irrespective of species or cell status. The levels of proline-rich protein (PRP) mRNA and parotid secretory protein (PSP) mRNA detected when using PRP cDNA of 600 bp and PSP cDNA of 805 bp for hybridization were higher in 2RSG cells than those in rat parotid glands; the reverse was observed in 2HPC8 cells and human parotid glands. The levels of PRP mRNA and PSP mRNA in 2HPC8 and 2PH1G acinar cells were similar. The level of mRNA was not detectable in murine neuroblastoma cells (NBP2) using the same alpha-amylase cDNA, PRP cDNA and PSP cDNA for hybridization. The PSP level in rat parotid gland was lower than that found in 2RSG cells; the reverse was observed in 2HPC8 cells and human parotid glands. The level of PSP in 2HP1G cells was higher than that found in 2HPC8 cells. Isoproterenol increased the cAMP level in 2RSG, 2HPC8, and 2HP1G clones, being most effective in 2RSG cells, and least effective in 2HPG cells. Prostaglandin E1 (PGE1) also increased cAMP level, being most effective in 2HPC8 cells and ineffective in 2HP1G cells, suggesting that the PGE1 receptor-linked adenylate cyclase becomes inactive upon transformation. These results suggest that the three clonal acinar cells from rat and human parotid glands reported here can be useful in comparative studies on regulation of growth, differentiation, and transformation.

Adenylyl Cyclases

Regulation of synaptic strength at mixed synapses: effects of dopamine receptor blockade and protein kinase C activation.

Previous studies of the mixed excitatory synapses between eighth nerve afferents and the lateral dendrite of the goldfish Mauthner (M-) cell have shown that synaptic strength is enhanced for an hour or longer following either repeated brief tetanizations or local extracellular applications of dopamine. Both the initial electrotonic coupling potential, mediated via current flow through gap junctions, and the subsequent chemically mediated excitatory postsynaptic potentials (EPSPs) are potentiated. Different second messenger pathways are implicated in the postsynaptic induction of these potentiations, with a Ca2+ influx presumably triggering the activity dependent long-term potentiations (LTP) and dopamine acting via a cAMP dependent pathway. Experiments performed to determine whether the LTP involves a stimulus-induced release of dopamine or requires a background level of dopamine receptor activation suggest neither is the case, as tetanization in the presence of a D1 receptor antagonist, which blocks the dopamine effects, produced an LTP comparable to that in the absence of the blocker. The effects of Ca2+ are presumably not due to protein kinase C (PKC) activation, since phorbol esters had no effect on the mixed excitatory synaptic responses, although they did enhance the frequency of spontaneously occurring inhibitory PSPs.

Animals

The antibody response in seabather's eruption.

Thirty-six of 44 patients with seabather's eruption had specific IgG antibodies against Linuche unguilata (thimble jelly) medusae antigen. ELISA detected antibodies in serum stored for 10 years. The extent of the cutaneous eruption or sting severity was correlated with antibody titer. Antibodies were detected in patients acquiring the eruption in Florida, the Bahamas and Aruba, reflecting the habitat of these jellyfish. This serological assay can be useful to confirm the clinical diagnosis.

Adult

Excess maternal history of diabetes in Caucasian and Afro-origin non-insulin-dependent diabetic patients suggests dominant maternal factors in disease transmission.

We examined the records of 2576 patients with non-insulin-dependent diabetes mellitus (NIDDM) and categorised them according to race and family history of diabetes. Family history of diabetes is known to play an important role in the development of NIDDM, and a maternal history is thought to be most influential. We found that a maternal history of diabetes was present in 60% of Caucasian and West Indian patients with a parental history of diabetes, whereas in Asian patients the figure was only 34%. Asian men were also more likely to have a father with diabetes. This anomaly may be due to cultural differences in the reporting of the disease. Our data support the dominant maternal role in the development of NIDDM in their offspring and suggest an under-reporting of NIDDM in Asian females.

Africa

A rapid test for measuring the infectivity of Yellow Fever vaccine.

An in-house reference preparation of 17D-204 Yellow Fever vaccine was tested 60 times using LD50 mouse assay and CCID50 method. The mean virus titre, standard deviation and coefficient of variation obtained were comparable. Student's t-test indicated that there was a statistically insignificant difference between the two methods (p > 0.05) used for potency test with a correlation coefficient of 0.666 (p < 0.05). CCID50 assay for measuring the infectivity of Yellow Fever vaccine is rapid, sensitive and reproducible.

Animals

Fine specificity of immune responses to epitopic sequences in synthetic peptides containing B and T epitopes from the conserved Plasmodium falciparum blood-stage antigens.

Immunisation with two chemically synthesised, linear, multiple epitope peptides (MEP) containing B and T cell epitopes from two conserved blood-stage antigens of the human malaria parasite, Plasmodium falciparum, induced high levels of circulating antibodies without the use of a carrier protein. Immunisation of BALB/c mice with MEP constructs (P1 and P2) induced antibodies against the various epitope sequences included in their structures, although the immune response was focused more towards the N terminal and the middle portion of the peptides. In vitro T cell proliferation assays indicated that only one of the two Th epitopes included in P1 and P2 are functional. Both P1 and P2, based on P. falciparum sequences, cross-reacted with sera from P. yoelii-infected mice. Immunisation with P1 in CFA, but not with P2, provided partial protection to BALB/c mice against P. yoelii challenge infection. Peptide P1 was highly immunogenic in alum also, and a somewhat higher level of protection was observed as compared to CFA immunisation. We found that immunisation with P1 induced antibody responses in different strains of mice, although to different extents. These results suggest that linear, multiple epitope peptides may offer attractive alternatives as subunit vaccine candidate molecules, but at the same time highlight the fact that the design principles are far from being clear and have yet to be worked out.

Amino Acid Sequence

Polyclonal antibody-based antigen-detection immunoassay for diagnosis of Trypanosoma evansi in buffaloes and horses.

An enzyme-linked immunosorbent assay (ELISA) was employed for the detection of Trypanosoma evansi antigens in serum samples of field cases of buffaloes and horses in northern India. In 323 naturally infected/suspected buffaloes, circulating antigenaemia was detected in 180 (55.72%), whereas parasitaemia by wet blood smear examination was found in 62 (19.19%) only. The antigen-ELISA was positive in 47 of the 62 parasitologically proven cases and in 86 of the 116 cases with anti-trypanosome antibodies detected by ELISA. Of the 80 horses examined antigen-ELISA was positive in 45 (56.75%) sera. The antigen-detection assay was positive in 14 of the 19 parasitaemic cases whereas the antibody-detection assay was positive in 18 of the 30 parasitaemic cases. In the present study, antigen-ELISA was found to be more sensitive and specific compared with antibody-ELISA and wet blood examination, and could prove a useful tool for epidemiological studies of latent trypanosomosis in livestock.

Animals

Reactions of diazines with nucleophiles--IV. The reactivity of 5-bromo-1,3,6-trimethyluracil with thiolate ions--substitution versus X-philic versus single electron transfer reactions.

Reaction of 5-Bromo-1,3,6-trimethyluracil (1) with alkylthiolate (propane-1-, toluene-alpha-, allyl-, etc.) ions under phase transfer catalytic conditions follows nucleophilic substitution and X-philic (Br and S) elimination to give 5-alkylthio-1,3,6-trimethyluracils, 6-alkylthiomethyl-1,3-dimethyluracils and 1,3,6-trimethyluracil. Reaction of compound 1 with heteroarylthiolate ions (pyridine-2-, quinazoline-4-, uracil-2- and 4,6-dimethylpyrimidine-2-thiolate) gives only nucleophilic substitution products. However, arylthiolate (phenyl-, 4-chlorophenyl-, 2-aminophenyl-) ions follow a single electron transfer (SET) mechanism to give 5-arylthio-6-arylthiomethyl-1,3-dimethyluracils along with normal substitution products. 1,3,6-Trimethyluracil does not react with alkyl- or heteroaryl-thiolate ions but reacts with arylthiolate ions (SET) providing mainly 5-arylthio-1,3,6-trimethyluracils.

Alkylation

Microorganisms cultured from the anterior chamber of ruptured globes at the time of repair.

PURPOSE: We studied events leading to the development of posttraumatic endophthalmitis by examining the significance of 15 factors on microbial contamination of injured eyes. METHODS: A prospective study was done of 30 ruptured globes in patients admitted to an urban medical center. Cultures were taken from the conjunctiva before and after preoperative disinfection and from the anterior chamber at the beginning and end of wound repair. Twenty-five of 30 patients received a three-day regimen of intravenous antibiotics that were begun before surgery. RESULTS: Anterior chamber samples grew microorganisms in ten (33%) of 30 eyes, with positive cultures recovered from specimens taken at the beginning of wound repair in eight eyes and at the end of wound repair in six eyes. Contamination with indigenous flora may have occurred at the time of injury in one eye and during repair in another eye. Microbes recovered included Staphylococcus, Corynebacterium, and Aspergillus species. No patient developed endophthalmitis. Of the 15 factors studied, only intravenous antibiotics significantly decreased the incidence of positive anterior chamber cultures in eyes treated before wound repair compared with eyes not receiving such therapy (P = .002). CONCLUSIONS: Despite the frequency of anterior chamber microbial contamination during injury or repair of the wound, with our treatment protocol and the presence of physiologic mechanisms to reduce intraocular microbes, no eyes developed clinical endophthalmitis. With our limited sample size only intravenous antibiotic therapy was found significantly to reduce anterior chamber microorganisms at the time of surgical repair, supporting their prophylactic use against the development of posttraumatic endophthalmitis.

Adult

Postural aberrations in low back pain.

The purpose of this study was to measure and describe postural aberrations in chronic and acute low back pain in search of predictors of low back pain. The sample included 59 subjects recruited to the following three groups: chronic, acute, or no low back pain. Diagnoses included disc disease, mechanical back pain, and osteoarthritis. Lumbar lordosis, thoracic kyphosis, head position, shoulder position, shoulder height, pelvic tilt, and leg length were measured using a photographic technique. In standing, chronic pain patients exhibited an increased lumbar lordosis compared with controls (p < .05). Acute patients had an increased thoracic kyphosis and a forward head position compared with controls (p < .05). In sitting, acute patients had an increased thoracic kyphosis compared with controls (p < .05). These postural parameters identified discrete postural profiles but had moderate value as predictors of low back pain. Therefore other unidentified factors are also important in the prediction of low back pain.

Acute Disease